Early detection and accurate diagnosis of breast cancer with screening and diagnostic mammography are critical aspects of breast cancer treatment as they lead to early intervention in the course of the disease, possibly before the cancer has spread. Mammography has been the primary imaging tool for screening and diagnostic work-up of breast cancer. It is well known that the sensitivity of mammography is substantially reduced in radiographic dense breasts. Adjunctive use of breast magnetic resonance imaging (MRI) is recommended for screening women with high-risk of breast cancer.
MRI uses a magnetic field and pulses of radio wave energy to image breasts. MRI is able to provide different information than can be imaged with an x-ray based method such as mammography. Thus, breast MRI plays a major role in diagnostic imaging. Key factors that contribute to the high sensitivity of breast MRI include the ability to provide three-dimensional (3-D) images of the breast, and more importantly, the use of intravenously injected Gadolinium contrast media enhances abnormalities associated with hypervascularity or tumor angiogenesis. However, cost and access are major limitations for MRI tests. Also, breast MRI scans have much lower spatial resolution than mammography.
Since mammography provides a 2-D image of the 3-D breast, superposition of structures leads to anatomic noise, which can mask lesions and/or mimic the presence of lesions that can lead to additional imaging and tissue biopsy.
Digital breast tomosynthesis is a technique where a number of 2-D x-ray projections are acquired over a limited angular range not exceeding 180 degrees (typically from 15 to 60 degrees). The acquired images are mathematically reconstructed to provide a quasi-tomographic 3-D image of the object. (Niklason, et al. 1997 Radiology 205 (2), 399-406.) This technique has the potential to improve detection and diagnosis of an abnormality by reducing the masking effect of superposed anatomy. (Suryanarayanan, et al. 2000 Acad Radiol 7 (12), 1085-1097; Suryanarayanan, et al. 2001 Acad Radiol 8 (3), 219-224.) A clinical breast tomosynthesis system recently received marketing approval from the FDA. (Selenia® Dimensions®, Hologic Inc., Bedford, Mass.) However, mammography and digital breast tomosynthesis systems that are currently used provide only anatomic images of the breast.
The clinical potential is being investigated for contrast enhanced digital mammography and contrast enhanced digital breast tomosynthesis, wherein iodinated contrast media is intravenously injected. (Jong, et al. 2003 Radiology 228 (3), 842-850; Lewin, et al. 2003 Radiology 229 (1), 261-268; Chen, et al. 2007 Acad Radiol 14 (2), 229-238; Puong, et al. Medical Imaging 2008: Physics of Medical Imaging San Diego, Calif., 2008 Proc. SPIE, Vol. 6913, pp. 69130Z (62008); DOI:69110.61117/69112.770148; Saunders, et al. Medical Imaging 2008: Physics of Medical Imaging San Diego, Calif., 2008 Proc. SPIE, Vol. 6913, pp. 69130Y (62008); DOI:69110.61117/69112.772042.) A major limitation of existing systems for contrast enhanced digital mammography and contrast enhanced digital breast tomosynthesis require repositioning of the subject, as the system is designed to image one breast at a time. This may result in the need for two injections that double the amount of injected contrast media, for bilateral exams.
In PCT/US12/22936 (by Vedantham and Karellas, expressly incorporated herein by referenced for all purposes), a tomosynthesis imaging system was disclosed for providing radiographic, stereoscopic and tomographic images of an object, such as the human breast. The system includes a high-fluence rate x-ray source and a plurality of satellite x-ray sources operating at lower fluence rate than the high-fluence rate source. A controller controls the operation and locations of the sources, and the operation of a detector. The method provides procedures in which the operation of the high-fluence source and the satellite sources are individually controlled as to location and orientation relative to the object of interest. In some operations, one satellite source may be operating while another satellite source may be repositioning. By proper control, a reduced x-ray dose and reduced operating time can be attained.
While there have been several studies on dynamic contrast enhanced breast MRI, Boetes reported their results with a temporal sampling of 2.3 seconds. (Kuhl, et al. 2000 J Magnetic Resonance Imaging 12 (6), 965-974; Boetes, et al. 1994 Radiology 193 (3), 777-781.) Even with this relatively coarse temporal sampling, they observed that malignant lesions started to enhance 11.5 seconds after contrast administration. Applying this criterion, they achieved a sensitivity and specificity of 95% and 86% respectively, in a cohort of 87 lesions.
Contrast enhanced digital mammography has been studied either using dual-energy technique wherein low and high-energy image pairs are acquired after administration of contrast media, or using temporal subtraction wherein pre-contrast image is acquired before contrast administration and post-contrast image(s) after contrast administration. (Lewin, et al. 2003 Radiology 229 (1), 261-268.) In a study on contrast-enhanced dual-energy digital mammography by Lewin et al., low and high-energy images were acquired 150 seconds after administration of contrast media. This method provided a singular time-point on contrast enhancement and did not provide for studying contrast enhancement kinetics. While it is possible to acquire multiple images at different time points after contrast administration, the temporal resolution of such an approach is limited by the frame-rate capabilities of the x-ray imaging detector. In another study, the first image after the start of contrast administration is acquired at 1 minute and subsequent images are acquired in 2 minutes interval. (Jong, et al. 2003 Radiology 228(3), 842-850.) Thus, the technique presents coarse temporal sampling of contrast enhancement kinetics.
U.S. Pat. No. 8,194,819 B2 (Eliasson), a mammography method system was disclosed that utilized two x-ray detectors in parallel on opposite sides of the support unit (facing away from each other) to generate x-ray images of the breasts.
In a contrast enhanced digital breast tomosynthesis study, post contrast image acquisition began 90 seconds after contrast administration and each of the nine projection images used to reconstruct the quasi-tomographic image was separated by 30 seconds. (Chen, et al. 2007 Acad Radiol 14 (2), 229-238.) Thus, the method takes 4.5 minutes to acquire the dataset that represents a single time point and hence suffers from substantial limitations on studying contrast enhancement kinetics.
Thus, there remains an ongoing need for alternatives to breast MRI that are cost-effective and provide better spatial and temporal resolution for visualizing abnormalities in the breast.